The contribution of absorption of integral nanocrystals to enhancement of oral bioavailability of quercetin  

作　　者：Baode Shen Chengying Shen Weifeng Zhu Hailong Yuan 

机构地区：[1]Department of Pharmacy,Air Force Medical Center,PLA,Beijing 100142,China [2]Key Lab of Modern Preparation of Traditional Chinese Medicine(TCM),Ministry of Education,Jiangxi University of TCM,Nanchang 330004,China

出　　处：《Acta Pharmaceutica Sinica B》2021年第4期978-988,共11页药学学报（英文版）

基　　金：supported by the National Natural Science Foundation of China(Nos.81803741 and 81873092)。

摘　　要：In this study,self-discriminating hybrid nanocrystals was utilized to explore the biological fate of quercetin hybrid nanocrystals(QT-HNCs)with diameter around 280 nm(QT-HNCs-280)and550 nm(QT-HNCs-550)following oral and intravenous administration and the contribution of integral nanocrystals to oral bioavailability enhancement of QT was estimated by comparing the absolute exposure of integral QT-HNCs and total QT in the liver.Results showed that QT-HNCs could reside in vivo as intact nanocrystals for as long as 48 h following oral and intravenous administration.A higher accumulation of integral QT-HNCs in liver and lung was observed for both oral and intravenous administration of QT-HNCs.The particle size affects the absorption and biodistribution of integral QT-HNCs and total QT.As compared to QT-HNCs-550,QT-HNCs-280 with smaller particle size is more easily absorbed,but dissolves faster in vivo,leading to higher distribution of QT(146.90 vs.117.91 h·mg/mL)but lower accumulation of integral nanocrystals(6.82 e10 vs.15.27 e10 h·[p/s]/[μW/cm2])in liver following oral administration.Due to its slower dissolution and enhanced recognition by RES,QT-HNCs-550 with larger diameter shows higher liver distribution for both of QT(1015.80 h·mg/mL)and integral nanocrystals(259.63 e10 h·[p/s]/[μW/cm2])than those of QT-HNCs-280(673.82&77.66 e10 h·[p/s]/[μW/cm2])following intravenous administration.The absolute exposure of integral QT-HNCs in liver following oral administration of QT-HNCs are 8.78%for QT-HNCs-280 and 5.88%for QT-HNCs-550,while the absolute exposure of total QT for QT-HNCs-280 and QT-HNCs-550 are 21.80%and 11.61%,respectively.Owing to imprecise quantifcation method,a surprisingly high contribution of integral QT-HNCs to oral bioavailability enhancement of QT(40.27%for QT-HNCs-280 and 50.65%for QT-HNCs-550)was obtained.These results revealed signifcant difference in absorption and biodistrbution between integral nanocrystals and overall drugs following oral and intravenous administration of QT-HNCs,and pr

关 键 词：NANOCRYSTALS Biological fate QUERCETIN PHARMACOKINETICS BIODISTRIBUTION Oral bioavailability CONTRIBUTION Drug delivery 

分 类 号：R943[医药卫生—药剂学] TQ460.4[医药卫生—药学] TB383.1[化学工程—制药化工]